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HDAC4 Gene

protein-coding   GIFtS: 73
GCID: GC02M239969

Histone Deacetylase 4

(Previous name: brachydactyly-mental retardation syndrome)
(Previous symbol: BDMR)
  See HDAC4-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Histone Deacetylase 41 2     Brachydactyly-Mental Retardation Syndrome1
BDMR1 2 5     HA61162
HD42 3     HDAC-42
EC 3.5.1.983 8     HDAC-A2
AHO32 5     Histone Deacetylase A2
HDACA2 5     KIAA02883

External Ids:    HGNC: 140631   Entrez Gene: 97592   Ensembl: ENSG000000680247   OMIM: 6053145   UniProtKB: P565243   

Export aliases for HDAC4 gene to outside databases

Previous GC identifers: GC02M237911 GC02M238543 GC02M239886 GC02M240182 GC02M239707 GC02M239634 GC02M231741


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for HDAC4 Gene:
Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events.
Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The
protein encoded by this gene belongs to class II of the histone deacetylase/acuc/apha family. It possesses
histone deacetylase activity and represses transcription when tethered to a promoter. This protein does not bind
DNA directly, but through transcription factors MEF2C and MEF2D. It seems to interact in a multiprotein complex
with RbAp48 and HDAC3. (provided by RefSeq, Jul 2008)

GeneCards Summary for HDAC4 Gene:
HDAC4 (histone deacetylase 4) is a protein-coding gene. Diseases associated with HDAC4 include 2q37 microdeletion syndrome, and cohen syndrome. GO annotations related to this gene include sequence-specific DNA binding and transcription factor binding. An important paralog of this gene is HDAC9.

UniProtKB/Swiss-Prot: HDAC4_HUMAN, P56524
Function: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A,
H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in
transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the
formation of large multiprotein complexes. Involved in muscle maturation via its interaction with the myocyte
enhancer factors such as MEF2A, MEF2C and MEF2D

summary for HDAC4 Gene:
Histone Deacetylases (HDACs) are a group of enzymes closely related to sirtuins. They catalyze the removal
of acetyl groups from lysine residues in histones and non-histone proteins, resulting in transcriptional
repression. In general, they do not act autonomously but as components of large multiprotein complexes, such
as pRb-E2F and mSin3A, that mediate important transcription regulatory pathways. There are three classes of
HDACs; classes 1, 2 and 4, which are closely related Zn2+-dependent enzymes. HDACs are ubiquitously
expressed and they can exist in the nucleus or cytosol. Their subcellular localization is effected by
protein-protein interactions (for example HDAC-14.3.3 complexes are retained in the cytosol) and by the
class to which they belong (class 1 HDACs are predominantly nuclear whilst class 2 HDACs shuttle between the
nucleus and cytosol). HDACs have a role in cell growth arrest, differentiation and death and this has led to
substantial interest in HDAC inhibitors as possible antineoplastic agents.

Gene Wiki entry for HDAC4 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000002.11  NT_005403.18  NC_018913.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the HDAC4 gene promoter:
         TBP   Egr-3   AML1a   p300   Cdc5   E4BP4   C/EBPalpha   S8   POU2F1   POU2F1a   
         Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids
   Search Chromatin IP Primers for HDAC4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat HDAC4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q37.3   Ensembl cytogenetic band:  2q37.3   HGNC cytogenetic band: 2q37.3

HDAC4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HDAC4 gene location

GeneLoc information about chromosome 2         GeneLoc Exon Structure

GeneLoc location for GC02M239969:  view genomic region     (about GC identifiers)

Start:
239,969,864 bp from pter      End:
240,323,348 bp from pter
Size:
353,485 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: HDAC4_HUMAN, P56524 (See protein sequence)
Recommended Name: Histone deacetylase 4  
Size: 1084 amino acids; 119040 Da
Subunit: Interacts with HDAC7 (By similarity). Homodimer. Homodimerization via its N-terminal domain. Interacts
with MEF2C, AHRR, and NR2C1. Interacts with a 14-3-3 chaperone protein in a phosphorylation dependent manner.
Interacts with BTBD14B (By similarity). Interacts with KDM5B. Interacts with MYOCD (By similarity). Interacts
with MORC2. Interacts with ANKRA2
Sequence caution: Sequence=BAA22957.2; Type=Erroneous initiation;
Selected PDB 3D structures from and Proteopedia for HDAC4 (see all 13):
2H8N (3D)        2O94 (3D)        2VQJ (3D)        2VQM (3D)        2VQO (3D)        2VQQ (3D)    
Secondary accessions: Q9UND6

Explore the universe of human proteins at neXtProt for HDAC4: NX_P56524

Explore proteomics data for HDAC4 at MOPED

Post-translational modifications: 

  • Phosphorylated by CaMK4 at Ser-246, Ser-467 and Ser-632. Phosphorylation at other residues by CaMK2D is required
    for the interaction with 14-3-3. Phosphorylation at Ser-350 impairs the binding of ANKRA2 but generates a
    high-affinity docking site for 14-3-31
  • Sumoylation on Lys-559 is promoted by the E3 SUMO-protein ligase RANBP2, and prevented by phosphorylation by CaMK41
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for HDAC4 (P56524) (see all 30)
     SGPSSPN  RVNHMPS  EYLAAFR  HHGNGTQ 


    See HDAC4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_006028.2  
    ENSEMBL proteins: 
     ENSP00000264606   ENSP00000410551   ENSP00000391226   ENSP00000405226   ENSP00000392912  
     ENSP00000438111   ENSP00000440481   ENSP00000443057  
    Reactome Protein details: P56524

    HDAC4 Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant HDAC4 Protein
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Protein for HDAC4
    OriGene Protein Over-expression Lysate for HDAC4
    OriGene MassSpec for HDAC4
    OriGene Custom Protein Services for HDAC4
    GenScript Custom Purified and Recombinant Proteins Services for HDAC4
    Novus Biologicals HDAC4 Proteins
    Novus Biologicals HDAC4 Lysates
    Sino Biological Recombinant Protein for HDAC4
    Sino Biological Cell Lysate for HDAC4
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for HDAC4

     
    Search eBioscience for Proteins for HDAC4 

    HDAC4 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of HDAC4
    R&D Systems Antibodies for HDAC4 (Histone Deacetylase 4/HDAC4)
    Cell Signaling Technology (CST) Antibodies for HDAC4 
    OriGene Antibodies for HDAC4
    OriGene Custom Antibody Services for HDAC4
    Novus Biologicals HDAC4 Antibodies
    Abcam antibodies for HDAC4 (Q9UKV0, P56524)
    Cloud-Clone Corp. Antibodies for HDAC4
    ThermoFisher Antibody for HDAC4
    LSBio Antibodies in human, mouse, rat for HDAC4

    HDAC4 Assay Products:

    EMD Millipore Kits and Assays for the Analysis of HDAC4
    OriGene Custom Assay Services for HDAC4
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for HDAC4
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for HDAC4
    Cloud-Clone Corp. CLIAs for HDAC4
    Search eBioscience for ELISAs for HDAC4 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    5 InterPro protein domains:
     IPR024643 Hist_deacetylase_Gln_rich_N
     IPR017320 Histone_deAcase_II_euk
     IPR000286 His_deacetylse
     IPR019154 Arb2_domain
     IPR023801 His_deacetylse_dom

    Graphical View of Domain Structure for InterPro Entry P56524

    ProtoNet protein and cluster: P56524

    1 Blocks protein domain: IPB000286 Histone deacetylase superfamily signature

    UniProtKB/Swiss-Prot: HDAC4_HUMAN, P56524
    Domain: The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm
    Similarity: Belongs to the histone deacetylase family. HD type 2 subfamily


    Find genes that share domains with HDAC4           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: HDAC4_HUMAN, P56524
    Function: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A,
    H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in
    transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the
    formation of large multiprotein complexes. Involved in muscle maturation via its interaction with the myocyte
    enhancer factors such as MEF2A, MEF2C and MEF2D
    Catalytic activity: Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone

         Enzyme Number (IUBMB): EC 3.5.1.981 2

         Gene Ontology (GO): Selected molecular function terms (see all 20):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001047core promoter binding IEA--
    GO:0003677DNA binding ----
    GO:0003714transcription corepressor activity IEA--
    GO:0004407histone deacetylase activity IDA10220385
    GO:0005515protein binding IPI10869435
         
    Find genes that share ontologies with HDAC4           About GenesLikeMe


    Phenotypes:
         2 GenomeRNAi human phenotypes for HDAC4:
     Increased cell death in breast  Prevent p53-dependent growth a 

         8 MGI mutant phenotypes (inferred from 3 alleles(MGI details for Hdac4):
     behavior/neurological  craniofacial  growth/size/body  integument  mortality/aging 
     muscle  nervous system  skeleton 

    Find genes that share phenotypes with HDAC4           About GenesLikeMe

    Animal Models:
         MGI mouse knock-out Hdac4tm1Eno for HDAC4

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for HDAC4
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for HDAC4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for HDAC4
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for HDAC4

    miRNA
    Products:
        
    miRTarBase miRNAs that target HDAC4:
    hsa-mir-1 (MIRT001053), hsa-mir-140-5p (MIRT000693), hsa-mir-22-3p (MIRT004035), hsa-mir-30c-5p (MIRT007109), hsa-mir-29b-3p (MIRT000096)

    Block miRNA regulation of human, mouse, rat HDAC4 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate HDAC4 (see all 145):
    hsa-miR-140-5p hsa-miR-106a hsa-miR-128 hsa-miR-3653 hsa-miR-208b hsa-miR-1243 hsa-miR-3649 hsa-miR-200b
    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for HDAC4
    Predesigned siRNA for gene silencing in human, mouse, rat HDAC4

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for HDAC4

    Clone
    Products:
         
    OriGene clones in human, mouse for HDAC4 (see all 6)
    OriGene ORF clones in mouse, rat for HDAC4
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: HDAC4 (NM_006037)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for HDAC4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat HDAC4
    Addgene plasmids for HDAC4 

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for HDAC4
    Browse ESI BIO Cell Lines and PureStem Progenitors for HDAC4 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for HDAC4


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    HDAC4_HUMAN, P56524: Nucleus. Cytoplasm. Note=Shuttles between the nucleus and the cytoplasm. Upon muscle cells
    differentiation, it accumulates in the nuclei of myotubes, suggesting a positive role of nuclear HDAC4 in muscle
    differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to
    its phosphorylation at Ser-246, Ser-467 and Ser-632 by CaMK4 and SIK1. The nuclear localization probably depends
    on sumoylation
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    cytoskeleton2
    cytosol2
    extracellular1

    Gene Ontology (GO): Selected cellular component terms (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000118histone deacetylase complex IDA11804585
    GO:0005634nucleus IDA10869435
    GO:0005737cytoplasm IDA10869435
    GO:0005829cytosol IEA--
    GO:0017053transcriptional repressor complex IDA11804585

    Find genes that share ontologies with HDAC4           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for HDAC4 About   (see all 22)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Signaling by NOTCH1 PEST Domain Mutants in Cancer
    Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants0.79
    Constitutive Signaling by NOTCH1 PEST Domain Mutants0.79
    Signaling by NOTCH1 PEST Domain Mutants in Cancer0.79
    Signaling by NOTCH1 t(7;9)(NOTCH1-M1580 K2555) Translocation Mutant0.79
    Signaling by NOTCH1 in Cancer0.79
    FBXW7 Mutants and NOTCH1 in Cancer0.79
    Signaling by NOTCH10.79
    NOTCH1 Intracellular Domain Regulates Transcription0.68
    2Immune response Function of MEF2 in T lymphocytes
    Development Role of HDAC and calcium calmodulin dependent kinase CaMK in control of skeletal myogenesis0.38
    Immune response Function of MEF2 in T lymphocytes0.38
    3Cell cycle
    Cell cycle0.59
    4Signaling by GPCR
    Signal Transduction0.58
    5p53 Signaling
    p53 Pathway0.38


    Find genes that share SuperPaths with HDAC4           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    1 Cell Signaling Technology (CST) Pathway for HDAC4
        Chromatin Regulation / Acetylation

    4 GeneGo (Thomson Reuters) Pathways for HDAC4
        Development Role of HDAC and calcium/calmodulin-dependent kinase (CaMK) in control of skeletal myogenesis
    Development Ligand-dependent activation of the ESR1/AP-1 pathway
    Immune response Function of MEF2 in T lymphocytes
    Signal transduction Calcium signaling

    Selected BioSystems Pathways for HDAC4 (see all 8)
        MicroRNAs in cardiomyocyte hypertrophy
    Cell cycle
    Neural Crest Differentiation
    Endochondral Ossification
    Signaling events mediated by HDAC Class III

    2 Sino Biological Pathways for HDAC4
        Notch Signaling Pathway
    p53 Pathway

    3 Reactome Pathways for HDAC4
        Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
    NOTCH1 Intracellular Domain Regulates Transcription
    Constitutive Signaling by NOTCH1 PEST Domain Mutants


    4 Kegg Pathways  (Kegg details for HDAC4):
        Alcoholism
    Epstein-Barr virus infection
    Viral carcinogenesis
    MicroRNAs in cancer

        Pathway & Disease-focused RT2 Profiler PCR Arrays including HDAC4 (see all 6): 
              Neurogenesis in human mouse rat
              Epigenetic Chromatin Modification Enzymes in human mouse rat
              Cancer Drug Targets in human mouse rat
              Nuclear Receptors & Coregulators in human mouse rat
              Inflammatory Response & Autoimmunity 384HT in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for HDAC4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for HDAC4 (P565241, 2, 3 ENSP000002646064) via UniProtKB, MINT, STRING, and/or I2D (see all 311)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HIST1H4LP628053, ENSP000003482584I2D: score=1 STRING: ENSP00000348258
    HIST1H4AP628053I2D: score=1 
    HIST1H4BP628053I2D: score=1 
    HIST1H4CP628053I2D: score=1 
    HIST1H4DP628053I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 33):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000122negative regulation of transcription from RNA polymerase II promoter IMP18850004
    GO:0001501skeletal system development IEA--
    GO:0002076osteoblast development IEA--
    GO:0006338chromatin remodeling IDA18850004
    GO:0006351transcription, DNA-templated IEA--

    Find genes that share ontologies with HDAC4           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
    Selected ApexBio Compounds for HDAC4 (see all 29)     About this table
    CompoundAction CAS #
    AR-42 (OSU-HDAC42)Pan-HDAC inhibitor[935881-37-1]
    Belinostat (PXD101)Novel and potent hydroxamate-type HDAC inhibitor[414864-00-9]
    CI994 (Tacedinaline)HDAC1 and 3 inhibitor[112522-64-2]
    CUDC-101Multitargeted HDAC inhibitor[1012054-59-9]
    CUDC-907PI3K and HDAC inhibitor[1339928-25-4]
    DroxinostatSelective HDAC inhibitor[99873-43-5]
    Entinostat (MS-275,SNDX-275)Entinostat inhibits HDAC1 and HDAC3 but not HDAC8[209783-80-2]
    ITF2357 (Givinostat)HDAC inhibitor, inhibits class I and class II HDACs[732302-99-7]
    JNJ-26481585Potent pan-HDAC inhibitor[875320-29-9]
    LAQ824 (NVP-LAQ824,Dacinostat)Novel and potent HDAC inhibitor[404951-53-7]

    Compounds for HDAC4 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    TCS HDAC6 20bSelective HDAC6 inhibitor[956154-63-5]
    LMK 235Selective HDAC4/HDAC5 inhibitor[1418033-25-6]
    Trichostatin AHistone deacetylase inhibitor[58880-19-6]
    TubacinHDAC6 inhibitor; inhibits alpha-tubulin deacetylation[1350555-93-9]
    Sodium 4-PhenylbutyrateHistone deacetylase inhibitor[1716-12-7]

    1 HMDB Compound for HDAC4    About this table
    CompoundSynonyms CAS #PubMed Ids
    Butyric acid1-Butyrate (see all 25)107-92-617258775

    2 DrugBank Compounds for HDAC4    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    2,2,2-TRIFLUORO-1-{5-[(3-PHENYL-5,6-DIHYDROIMIDAZO[1,2-A]PYRAZIN-7(8H)-YL)CARBONYL]THIOPHEN-2-YL}ETHANE-1,1-DIOL-- --target--10592235
    N-hydroxy-5-[(3-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)carbonyl]thiophene-2-carboxamide-- --target--10592235

    10 Novoseek inferred chemical compound relationships for HDAC4 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    trapoxin 78 1 11134513 (1)
    lysine 43.1 2 16166628 (1), 19251700 (1)
    threonine 35.3 3 11114188 (1)
    serine 29.1 5 15205465 (1), 11114188 (1), 11390982 (1)
    butyrate 20 1 20383178 (1)
    calcium 16.9 21 12663674 (3), 10825153 (3), 18332106 (2), 16767219 (2) (see all 11)
    alanine 16.7 3 20188095 (1), 18045992 (1)
    zinc 14.5 2 18614528 (1), 19355988 (1)
    retinoid 7.48 1 17383980 (1)
    glutamate 0 1 15205465 (1)



    Find genes that share compounds with HDAC4           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for HDAC4 gene: 
    NM_006037.3  

    Unigene Cluster for HDAC4:

    Histone deacetylase 4
    Hs.20516  [show with all ESTs]
    Unigene Representative Sequence: NM_006037
    18 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000345617(uc010fyy.3 uc002vyk.4) ENST00000430200 ENST00000494800
    ENST00000487617 ENST00000463007(uc010fyz.1) ENST00000495497 ENST00000493582(uc010fza.2)
    ENST00000535493(uc010zoa.1) ENST00000460235 ENST00000461113(uc010fzb.1)
    ENST00000445704 ENST00000553145 ENST00000454542 ENST00000446876 ENST00000496347
    ENST00000544989 ENST00000543185 ENST00000541256(uc010znz.1)
    miRNA
    Products:
         
    Block miRNA regulation of human, mouse, rat HDAC4 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate HDAC4 (see all 145):
    hsa-miR-140-5p hsa-miR-106a hsa-miR-128 hsa-miR-3653 hsa-miR-208b hsa-miR-1243 hsa-miR-3649 hsa-miR-200b
    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
    Products:
         
    OriGene RNAi products in human, mouse, rat for HDAC4
    Predesigned siRNA for gene silencing in human, mouse, rat HDAC4
    Clone
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    OriGene clones in human, mouse for HDAC4 (see all 6)
    OriGene ORF clones in mouse, rat for HDAC4
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: HDAC4 (NM_006037)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for HDAC4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat HDAC4
    Addgene plasmids for HDAC4 
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    Additional mRNA sequence: 

    AB006626.2 AF070607.1 AF132607.1 AK302719.1 AK303368.1 AK303467.1 AK303617.1 AK308791.1 
    AK310488.1 AK310603.1 AK311582.1 BC039904.1 

    14 DOTS entries:

    DT.315082  DT.95176516  DT.97794529  DT.92056881  DT.120978132  DT.91785600  DT.95189639  DT.100831917 
    DT.95131879  DT.95352125  DT.95365884  DT.99969378  DT.100728217  DT.95365888 

    Selected AceView cDNA sequences (see all 115):

    AI491868 AW072681 AI823559 AF132607 AI801599 AB006626 BM676799 BF448234 
    CR607186 AI198969 AJ707294 BC039904 NM_006037 AI498343 CR625452 AL043738 
    AI342576 AI186037 BG574696 AA350265 AA948549 AW084671 BV200078 AI654062 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    HDAC4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ACATTTGCAG
    HDAC4 Expression
    About this image


    HDAC4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 3) fully expand
     
     Bone (Muscoskeletal System)    fully expand to see all 3 entries
             Prehypertrophic Chondrocytes Autopod Growth Plate
     
     Cartilage (Muscoskeletal System)    fully expand to see all 3 entries
             Prehypertrophic Chondrocytes Autopod Growth Plate
     
     Thymus (Hematopoietic System)
             Thymus
    HDAC4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    HDAC4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.20516

    UniProtKB/Swiss-Prot: HDAC4_HUMAN, P56524
    Tissue specificity: Ubiquitous

        Pathway & Disease-focused RT2 Profiler PCR Arrays including HDAC4 (see all 6): 
              Neurogenesis in human mouse rat
              Epigenetic Chromatin Modification Enzymes in human mouse rat
              Cancer Drug Targets in human mouse rat
              Nuclear Receptors & Coregulators in human mouse rat
              Inflammatory Response & Autoimmunity 384HT in human mouse rat

    Primer
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of eukaryotes.

    Orthologs for HDAC4 gene from Selected species (see all 17)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Hdac41 , 5 histone deacetylase 41, 5 86.43(n)1
    94.45(a)1
      1 (46.24 cM)5
    2087271  NM_207225.11  NP_997108.11 
     919327345 
    chicken
    (Gallus gallus)
    Aves HDAC41 histone deacetylase 4 81.51(n)
    91.1(a)
      374207  NM_204313.1  NP_989644.1 
    lizard
    (Anolis carolinensis)
    Reptilia HDAC46
    histone deacetylase 4
    84(a)
    1 ↔ 1
    1(118435072-118562758)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia hdac41 histone deacetylase 4 71.46(n)
    82.11(a)
      100489340  XM_004917886.1  XP_004917943.1 
    zebrafish
    (Danio rerio)
    Actinopterygii wufc56f082 wufc56f08 82.59(n)   325153  57051044 
    fruit fly
    (Drosophila melanogaster)
    Insecta HDAC43 histone deacetylase 57(a)   11E8   --
    worm
    (Caenorhabditis elegans)
    Secernentea hda-43 Expression: mu_bod, hypodermal, seam
    cells, amphid more
    50(a)
    (best of 2)
      X(16771247-16775220)   --
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes HDA16
    Putative catalytic subunit of a class II histone d...
    11(a)
    1 → many
    XIV(593227-595347) YNL021W
    rice
    (Oryza sativa)
    Liliopsida Os.213992 Oryza sativa (japonica cultivar-group) putative histone more 72.29(n)    AK111557.1 


    ENSEMBL Gene Tree for HDAC4 (if available)
    TreeFam Gene Tree for HDAC4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for HDAC4 gene
    HDAC92  HDAC62  HDAC52  HDAC72  HDAC102  
    8 SIMAP similar genes for HDAC4 using alignment to 9 protein entries:     HDAC4_HUMAN (see all proteins):
    MGC16025    HDAC9    KIAA0600    HDAC7    HDAC5    DKFZp779K1053
    DKFZp586I031    HDAC6

    Find genes that share paralogs with HDAC4           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for HDAC4 (see all 8442)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 2 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0360424
    A breast cancer sample4--see VAR_0360422 P R mis40--------
    rs1849061381,2
    --239355787(+) TTAGTA/CACTGG 1 -- ds50010--------
    rs745790981,2
    C,F--239355812(+) GAAGGG/AGCGCT 1 -- ds50012Minor allele frequency- A:0.10CSA WA 120
    rs1401749401,2
    --239355884(+) CTGTGC/GGCAGG 1 -- ds50010--------
    rs726208471,2
    C,F--239355954(+) AGCTCT/ACTATG 1 -- ds50018Minor allele frequency- A:0.32WA NA CSA EA 367
    rs1433635791,2
    C--239355965(+) TTGGT-/TAAGTG 1 -- ds50010--------
    rs1896213991,2
    --239356073(+) CCTGCC/GGCTGG 1 -- ds50010--------
    rs752514321,2
    C,F--239356189(+) GAGCCA/GATGAG 1 -- ds50011Minor allele frequency- G:0.09WA 118
    rs1177090691,2
    C,F--239356203(+) GAGAGC/TGCACG 1 -- ds50011Minor allele frequency- T:0.01EA 120
    rs1168009011,2
    C,F--239356239(+) AGTAAC/TGCAGT 1 -- ut311Minor allele frequency- T:0.02WA 118

    HapMap Linkage Disequilibrium report for HDAC4 (239969864 - 240219864 bp, first 250kb of HDAC4)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for HDAC4 (see all 69):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2721804CNV Deletion23290073
    esv2721827CNV Deletion23290073
    esv2721820CNV Deletion23290073
    esv2721805CNV Deletion23290073
    esv2668246CNV Deletion23128226
    esv2721803CNV Deletion23290073
    esv2721812CNV Deletion23290073
    esv2721828CNV Deletion23290073
    esv2721802CNV Deletion23290073
    esv2667661CNV Deletion23128226

    Human Gene Mutation Database (HGMD): HDAC4
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing HDAC4
    DNA2.0 Custom Variant and Variant Library Synthesis for HDAC4

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 605314   
    OMIM disorders: 600430  
    UniProtKB/Swiss-Prot: HDAC4_HUMAN, P56524
  • Brachydactyly-mental retardation syndrome (BDMR) [MIM:600430]: A syndrome resembling the physical
    anomalies found in Albright hereditary osteodystrophy. Common features are mild facial dysmorphism, congenital
    heart defects, distinct brachydactyly type E, mental retardation, developmental delay, seizures, autism spectrum
    disorder, and stocky build. Soft tissue ossification is absent, and there are no abnormalities in parathyroid
    hormone or calcium metabolism. Note=The disease is caused by mutations affecting the gene represented in this
    entry

  • 6 diseases for HDAC4:    
    About MalaCards
    2q37 microdeletion syndrome    cohen syndrome    brachydactyly type e    brachydactyly
    albright's hereditary osteodystrophy    neuronal intranuclear inclusion disease

    2 diseases from the University of Copenhagen DISEASES database for HDAC4:
    Brachydactyly     Hodgkin's lymphoma

    Find genes that share disorders with HDAC4           About GenesLikeMe

    5 Novoseek inferred disease relationships for HDAC4 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    cardiac hypertrophy 34.8 3 17179159 (2), 17038545 (1)
    hypertrophy 29.2 6 19716643 (2), 15537533 (1), 16767219 (1), 19704004 (1) (see all 5)
    cancer 16.5 11 18850004 (2), 19888759 (2), 17363583 (1), 19649663 (1) (see all 8)
    tumors 15.4 14 19622775 (6), 18850004 (1), 18227124 (1), 19956841 (1) (see all 8)
    leukemia 13.2 3 16409557 (1), 20393011 (1)

    Genetic Association Database (GAD): HDAC4
    Human Genome Epidemiology (HuGE) Navigator: HDAC4 (6 documents)

    Export disorders for HDAC4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for HDAC4 gene, integrated from 10 sources (see all 286):
    (articles sorted by number of sources associating them with HDAC4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Three proteins define a class of human histone deacetylases related to yeast Hda1p. (PubMed id 10220385)1, 2, 3, 9 Grozinger C.M.... Schreiber S.L. (Proc. Natl. Acad. Sci. U.S.A. 1999)
    2. Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome, with brachydactyly type E, developmental delays, and behavioral problems. (PubMed id 20691407)1, 2, 3 Williams S.R.... Elsea S.H. (Am. J. Hum. Genet. 2010)
    3. HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor. (PubMed id 10523670)1, 2, 9 Wang A.H.... Yang X.-J. (Mol. Cell. Biol. 1999)
    4. Nuclear calcium/calmodulin-dependent protein kinase IIdelta preferentially transmits signals to histone deacetylase 4 in cardiac cells. (PubMed id 17179159)1, 2, 9 Little G.H.... Poizat C. (J. Biol. Chem. 2007)
    5. The modular nature of histone deacetylase HDAC4 confers phosphorylation-dependent intracellular trafficking. (PubMed id 11470791)1, 2, 9 Zhao X.... Yao T.-P. (J. Biol. Chem. 2001)
    6. Regulation of histone deacetylase 4 by binding of 14-3-3 proteins. (PubMed id 10958686)1, 2, 9 Wang A.H.... Yang X.-J. (Mol. Cell. Biol. 2000)
    7. A new family of human histone deacetylases related to Saccharomyces cerevisiae HDA1p. (PubMed id 10206986)1, 3, 9 Fischle W....Verdin E. (J. Biol. Chem. 1999)
    8. HDAC4 deacetylase associates with and represses the MEF2 transcription factor. (PubMed id 10487761)1, 2, 9 Miska E.A....Kouzarides T. (EMBO J. 1999)
    9. Involvement of histone deacetylation in MORC2-mediated down- regulation of carbonic anhydrase IX. (PubMed id 20110259)1, 2, 9 Shao Y.... Li F. (Nucleic Acids Res. 2010)
    10. High throughput SNP and expression analyses of candidate genes for non-syndromic oral clefts. (PubMed id 16415175)1, 4, 9 Park J.W....Beaty T.H. (J. Med. Genet. 2006)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 9759 HGNC: 14063 AceView: HDAC4 Ensembl:ENSG00000068024 euGenes: HUgn9759
    ECgene: HDAC4 Kegg: 9759 H-InvDB: HDAC4

    (According to HUGE)
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    HUGE: KIAA0288

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for HDAC4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for HDAC4 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for HDAC4 gene:
    Search GeneIP for patents involving HDAC4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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